The Brain Changes in Sleep Apnea Study

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Sleep is critical to human health, but insufficient and disrupted sleep caused by sleep apnea are common and have a major impact on brain health. However, there is still much that is not known about how sleep apnea damages the brain and what can be done to fix this. The Brain Changes in Sleep Apnea Study will look at the brain health of people with severe sleep apnea both before and after 4 months of treatment with a CPAP machine. Pre- and post-CPAP treatment, 80 participants with severe sleep apnea will undergo cognitive testing, blood and urine tests, a pulse wave velocity test, and an MRI. Also pre- and post-CPAP treatment, participants will wear a blood pressure monitor for 24 hours, wear an accelerometer watch for 7 days to track the duration and quality of their sleep, and wear a device for 1 night of sleep to assess their breathing and blood oxygen levels. It is expected that there will be improvements in participants' brain health after 4 months of CPAP treatment.

Condition or disease

Intervention/treatment

SleepSleep ApneaSleep Apnea Syndromes

Diagnostic Test: Brain MRI, cognitive testing, bloodwork

Detailed Description:

Between January 2018 and February 2020, the Brain Changes in Sleep Apnea Study will recruit 80 adults with newly diagnosed severe sleep apnea attending the sleep clinics at Sunnybrook Health Sciences Centre (n=40) or the University of Edinburgh (n=40). Participants will undergo home-based assessment with 3 wearable devices (24 hours of ambulatory blood pressure monitoring, 7 days of actigraphy to assess sleep duration and fragmentation, and 1 night of finger-probe peripheral arterial tonometry and oximetry to assess cardiorespiratory physiology including sleep apnea), completion of a sleep and health questionnaire, 24-hour collection of urine for assessing sympathetic nervous system activity, blood banking for endothelial biomarkers, cognitive evaluation, pulse wave velocity test, and an MRI of the brain, at 2 time points: 1) after initial polysomnographic diagnosis of sleep apnea but before the initiation of CPAP, and 2) after 4 months of CPAP treatment.

Participants will undergo 3-Tesla MRI. Scan time will be about 1 hour and 15 minutes per subject per session at the Sunnybrook site. The protocol is designed to image SVD burden by quantifying PVS and WMH volumes, and image various physiological estimates on the brain.

Blood samples will be assayed for inflammatory and endothelial function. Classical vascular risk factors will also be assessed. Once data collection is complete, DNA will be extracted from the frozen PBMC fraction and will be genotyped for APOE genotype and a panel of other single nucleotide polymorphisms known to be associated with cognition and cerebrovascular disease.

We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on DTI fractional anisotropy on voxel-wise basis.

Change from baseline in a summary measure of arterial pulsatility [ Time Frame: Baseline and 4 months ]

We will use repeated measures linear mixed effect models to estimate the main effect of CPAP (i.e. compare pre- and post-CPAP measurements) on arterial pulsatility (as measured by the pulse wave velocity test).

We will quantify the main effect of CPAP treatment on cognitive performance (as measured by our computerized battery, which includes the MoCA, BNA-R, and BrainScreen).

Biospecimen Retention: Samples With DNA

Phlebotomy will be performed following an overnight fast, and samples will be banked for assessment of cytokines and endothelial biomarkers. Blood samples (25-30 ml) will be collected in plasma vacutainer tubes. Plasma will be separated and preserved in a freezer. The peripheral blood mononuclear cell (PBMC) fraction will also be kept in a freezer for genetic evaluation. All samples will be de-identified and preserved at -80oC and assayed together in a batch after the collection of the last sample (in 2020). Samples will be assayed for inflammatory and endothelial function by ELISA. Classical vascular risk factors will also be assessed.

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Ages Eligible for Study:

18 Years and older (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

80 adults with newly diagnosed severe sleep apnea will be recruited from the sleep clinics at Sunnybrook Health Sciences Centre (n=40) or the University of Edinburgh (n=40).

Criteria

Inclusion Criteria:

Newly diagnosed sleep apnea not on CPAP or any other treatment for sleep apnea;

Apnea hypopnea index >=15 on diagnostic polysomnogram;

O2 saturation in sleep <90% for >30 minutes;

Subjectively sleepy;

Planning on starting CPAP for sleep apnea.

Exclusion Criteria:

Known history of stroke, transient ischemic attack, or other CNS disease;